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Mitochondria as emerging targets for therapies against T cell acute lymphoblastic leukemia
Author(s) -
OlivasAguirre Miguel,
Pottosin Igor,
Dobrovinskaya Oxana
Publication year - 2019
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.5vmr0818-330rr
Subject(s) - vdac1 , voltage dependent anion channel , biology , mitochondrion , cancer research , programmed cell death , reactive oxygen species , oxidative stress , apoptosis , oxidative phosphorylation , microbiology and biotechnology , immunology , biochemistry , gene , escherichia coli , bacterial outer membrane
Acute lymphoblastic leukemia (ALL) comprises a heterogeneous group of hematologic malignancies, arising from diverse genetic alterations in the early lymphocyte development. T‐cell subtype of ALL (T‐ALL) accounts for about 15% and 25% of ALL in children and adults, respectively. Being less frequent among ALL subtypes, T‐ALL represents a high‐risk factor for poor prognosis due to its aggressiveness and resistance to common antileukemic drugs. Mitochondria were widely explored recently as a target for anticancer treatment because they are involved in a metabolic reprogramming of a cancer cell and play key roles in reactive oxygen species generation, Ca 2+ signaling, and cell death induction. Accordingly, a new class of anticancer compounds named mitocans has been developed, which target mitochondria at distinct crucial points to promote their dysfunction and subsequent cell death. The present review analyses the role of mitochondria in malignant reprogramming and emerging therapeutic strategies targeting mitochondria as an “Achilles’ heel” in T‐ALL, with an emphasis on BH3 mimetics, sequestering pro‐survival BCL proteins and voltage‐dependent anion channel (VDAC)1‐directed drugs, which promote the suppression of aerobic glycolysis, VDAC1 closure, mitochondrial Ca 2+ overload, stoppage of the oxidative phosphorylation, oxidative stress, and release of proapoptotic factors.